TRIM8 驱动的神经干细胞转录组特征鉴定出与神经胶质瘤相关的节点基因和通路。
TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways.
机构信息
Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy; Experimental and Regenerative Medicine, University of Foggia, Via A. Gramsci, 89/91, 71122, Foggia, Italy.
Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013, San Giovanni Rotondo, Foggia, Italy.
出版信息
Biochim Biophys Acta Gen Subj. 2019 Feb;1863(2):491-501. doi: 10.1016/j.bbagen.2018.12.001. Epub 2018 Dec 5.
BACKGROUND
We recently reported TRIM8, encoding an E3 ubiquitin ligase, as a gene aberrantly expressed in glioblastoma whose expression suppresses cell growth and induces a significant reduction of clonogenic potential in glioblastoma cell lines.
METHODS
we provided novel insights on TRIM8 functions by profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells by RNA-sequencing and bioinformatic analysis. Functional analysis including luciferase assay, western blot, PCR arrays, Real time quantitative PCR were performed to validate the transcriptomic data.
RESULTS
Our study identified enriched pathways related to the neurotransmission and to the central nervous system (CNS) functions, including axonal guidance, GABA receptor, Ephrin B, synaptic long-term potentiation/depression, and glutamate receptor signalling pathways. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3.
CONCLUSIONS
Our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different CNS-related pathways, including JAK-STAT.
GENERAL SIGNIFICANCE
This study provides novel insights on the physiological TRIM8 function by profiling for the first time the primary Neural Stem Cell over-expressing TRIM8 by using RNA-Sequencing methodology.
背景
我们最近报道了 TRIM8，它是一种编码 E3 泛素连接酶的基因，在神经胶质瘤中异常表达，其表达抑制细胞生长，并显著降低神经胶质瘤细胞系的克隆形成潜力。
方法
我们通过 RNA-seq 和生物信息学分析对表达 TRIM8 的原代小鼠胚胎神经干细胞进行了转录组分析，为 TRIM8 的功能提供了新的见解。通过荧光素酶测定、Western blot、PCR 阵列、实时定量 PCR 等功能分析验证了转录组数据。
结果
我们的研究确定了与神经传递和中枢神经系统 (CNS) 功能相关的富集途径，包括轴突导向、GABA 受体、Ephrin B、突触长时程增强/抑制和谷氨酸受体信号通路。最后，我们提供了关于 TRIM8 和 STAT3 之间存在功能交互串扰的额外证据。
结论
我们的结果通过使用 RNA-seq 方法首次对过表达 TRIM8 的原代神经干细胞进行了分析，证实了 TRIM8 在大脑功能中的作用，其通过调节不同与 CNS 相关的途径中的基因，包括 JAK-STAT。
一般意义
本研究通过使用 RNA-seq 方法首次对过表达 TRIM8 的原代神经干细胞进行了分析，为 TRIM8 的生理功能提供了新的见解。
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